Impairing tumor metabolic plasticity via a stable metal‐phenolic based polymeric nanomedicine to suppress colorectal cancer
File(s)
Supporting information
Author(s)
Type
Journal Article
Abstract
Targeting metabolic vulnerability of tumor cells is a promising anti-cancer strategy. However, the therapeutic efficacy of existing metabolism-regulating agents is often compromised due to tolerance resulting from tumor metabolic plasticity, as well as their poor bioavailability and tumor-targetability. Inspired by the inhibitive effect of N-ethylmaleimide on the mitochondrial function, we developed a dendronized polymer-functionalized metal-phenolic nanomedicine (pOEG-b-D-SH@NP) encapsulating N-ethylmaleimide-modified doxorubicin (Mal-DOX) to enable improvement in the overall delivery efficiency and inhibition of the tumor metabolism via multiple pathways. We observe that Mal-DOX and its derived nanomedicine induce energy depletion of CT26 colorectal cancer cells more efficiently than doxorubicin, and shifts the balance of programmed cell death from apoptosis toward necroptosis. Notably, pOEG-b-D-SH@NP simultaneously inhibits cellular oxidative phosphorylation and glycolysis, thus potently suppressing cancer growth and peritoneal intestinal metastasis in mouse models. Overall, the study provides a promising dendronized polymer-derived nano-platform for the treatment of cancers through impairing metabolic plasticity. This article is protected by copyright. All rights reserved.
Date Issued
2023-06-08
Date Acceptance
2023-03-01
Citation
Advanced Materials, 2023, 35 (23), pp.1-14
ISSN
0935-9648
Publisher
Wiley
Start Page
1
End Page
14
Journal / Book Title
Advanced Materials
Volume
35
Issue
23
Copyright Statement
© 2023 Wiley-VCH GmbH. All rights reserved. This is the peer reviewed version of the following article: Li, X., Duan, Z., Chen, X., Pan, D., Luo, Q., Gu, L., Xu, G., Li, Y., Zhang, H., Gong, Q., Chen, R., Gu, Z. and Luo, K. (2023), Impairing Tumor Metabolic Plasticity Via a Stable Metal-Phenolic Based Polymeric Nanomedicine to Suppress Colorectal Cancer. Adv. Mater.. Accepted Author Manuscript 2300548., which has been published in final form at https://doi.org/10.1002/adma.202300548. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36917817
Subjects
dendronized polymer
glycolysis
nanomedicine
oxidative phosphorylation
tumor metabolic plasticity
Publication Status
Published
Coverage Spatial
Germany
Date Publish Online
2023-03-14